Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007-2008

Background: Limited animal, in vitro, and human studies have reported that exposure to phthalates or bisphenol A (BPA) may affect thyroid signaling.Objective: We explored the cross-sectional relationship between urinary concentrations of metabolites of di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and BPA with a panel of serum thyroid measures among a representative sample of U.S. adults and adolescents.Methods: We analyzed data on urinary biomarkers of exposure to phthalates and BPA, serum thyroid measures, and important covariates from 1,346 adults (ages ≥ 20 years) and 329 adolescents (ages 12–19 years) from the National Health and Nutrition Examination Survey (NHANES) 2007–2008 using multivariable linear regression.Results: Among adults, we observed significant inverse relationships between urinary DEHP metabolites and total thyroxine (T₄), free T₄, total triiodothyronine (T₃), and thyroglobulin, and positive relationships with thyroid-stimulating hormone (TSH). The strongest and most consistent relationships involved total T₄, where adjusted regression coefficients for quintiles of oxidative DEHP metabolites displayed monotonic dose-dependent decreases in total T₄ (p-value for trend < 0.0001). Suggestive inverse relationships between urinary BPA and total T₄ and TSH were also observed. Conversely, among adolescents, we observed significant positive relationships between DEHP metabolites and total T₃. Mono(3-carboxypropyl) phthalate, a secondary metabolite of both DBP and di-n-octyl phthalate, was associated with several thyroid measures in both age groups, whereas other DBP metabolites were not associated with thyroid measures.Conclusions: These results support previous reports of associations between phthalates—and possibly BPA—and altered thyroid hormones. More detailed studies are needed to determine the temporal relationships and potential clinical and public health implications of these associations.     

Prenatal Bisphenol A exposure and early childhood neurodevelopment in Shandong,China

BackgroundSeveral epidemiological studies suggest that prenatal exposure to BPA may interfere with the neurodevelopment of pre-school and school-age children. However, a limited number of studies are available for effects during children at a younger age, especially in China.MethodsBased on Laizhou Wan Birth Cohort (LWBC), BPA concentrations were measured in urine among 506 pregnant women during their hospital admission for delivery and neurodevelopment of their children was assessed using the Gesell Development Schedules at 12 months (n = 368) and 24 months (n = 296). Linear regression and generalized linear models were used to analyze the association between prenatal BPA exposure and the children's developmental quotient scores (DQs).ResultsThe median of maternal BPA concentration was 0.48 μg/L or 1.05 μg/g creatinine. Maternal BPA concentrations were adversely associated with children DQs at 12 months of age, with a 10-fold increase in prenatal BPA concentrations correlated to 1.43-point decrease in DQs in the adaptive domain (β = ?1.43; 95% CI: ?2.30 to ?0.56, p = 0.001). When stratified by gender, prenatal BPA concentrations were adversely associated with the adaptive domain DQs among boys (p-trend = 0.012) and girls (p-trend = 0.028) and the social domain DQs (p-trend = 0.019) only among girls. At 24 months of age, the significant adverse association was only found in the language domain among girls (β = ?1.69; 95% CI: ?3.23 to ?0.15, p = 0.032).ConclusionBased on a Chinese population, we found potential impacts of prenatal BPA exposure on childhood neurodevelopment at 12 and 24 months of age, especially among girls.     

Gender differences in the associations between urinary bisphenol A and body composition among American children: The National Health and Nutrition Examination Survey, 2003–2006

Background

As an endocrine disruptor, bisphenol A (BPA) exposure has been implicated as a potential risk factor in childhood obesity, which is defined using percentiles of body mass index for age. We aimed to examine the associations between BPA exposure, reflected by urinary BPA concentration, and body composition in American children.

Factors Associated with Exposure to Dietary Bisphenols in Adolescents

Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25–9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03–7.67) in comparison with girls with a BMI lower than 25 kg/m². Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.     

Phthalate metabolites and bisphenol A in urines from German school-aged children: Results of the Duisburg Birth Cohort and Bochum Cohort Studies

Some phthalates and also bisphenol A (BPA) interfere with the human endocrine system and are labelled as reproductive toxicants. Children's exposure to these contaminants is suspected to be associated with developmental disorders and other health impairments.We provide biomonitoring data on 21 urinary phthalate metabolite and BPA levels in first morning urine of 8–10 year old children. Participants were children born between 1999 and 2002 of the Duisburg birth cohort (8–9 years, N = 113) and of the Bochum cohort study (8–10 years, N = 352). Additionally, for the Duisburg birth cohort we compare current data of children from Duisburg (8–9 years) with data from 2 years earlier when the children were 6–7 years old. We analyzed influences of important covariates on exposure levels by multiple regression analysis and those from two sampling time points by generalized equation estimation models adjusted for important covariates. Compared to recently published studies the phthalate metabolite and BPA concentrations were within the range of background levels. There were no significant differences between children from Bochum and Duisburg. Comparison between the two Duisburg birth cohort data sets (2007–2008 and 2009–2010) showed significant correlations for most of the phthalate metabolites (r_Spearman between 0.25 and 0.51; p ≤ 0.05) but not for BPA (r_Spearman= 0.162; p = 0.143). Most of the phthalate metabolites in the groups of the 6–7 and 8–9 years old Duisburg children were negatively associated with higher age, except for BPA concentrations with nearly constant levels. Exposure levels may be influenced by changes in child specific exposure patterns with age but also by the rapidly changing phthalate market.     

双酚A暴露水平与学龄期女童特发性性早熟风险之间的关系

目的 分析学龄女童接触双酚A(BPA)与特发性中枢性性早熟(ICPP)之间的关系,为预防女童特发性性早熟提供依据。方法 选取2016年7月-2018年9月于扬州大学附属医院就诊且被诊断为ICPP的110例6～9岁女童为研究对象。根据女童的年龄和体重指数(BMI)相匹配,选取110名健康女童作为对照组。检测所有女童尿BPA浓度,并测试其与ICPP风险的关系。实验室检查包括血清雌二醇(E2)水平,基础和促性腺激素释放激素(GnRH)刺激的促黄体激素(LH),促卵泡激素(FSH)水平,骨龄(BA),子宫和卵巢大小。结果 ICPP组和对照组的尿BPA中位数浓度分别为6.25 μg/g Cr和1.07 μg/g Cr(Z=-3.845,P<0.001)。调整混杂因素后,与BPA浓度最低的女童相比,最高浓度女童ICPP风险是其9.07倍(OR=9.07,95％CI:2.82～29.14) 。在ICPP组中,尿BPA浓度与FSH基础水平(r=-0.235,P=0.005)或FSH峰值水平(r=-0.171,P=0.044)呈负相关。结论 BPA暴露与学龄女童ICPP风险升高有关,潜在的机制可能归因于相对较低的FSH水平。     

双酚A暴露水平与学龄期女童特发性性早熟风险之间的关系

目的 分析学龄女童接触双酚A(BPA)与特发性中枢性性早熟(ICPP)之间的关系,为预防女童特发性性早熟提供依据。方法 选取2016年7月-2018年9月于扬州大学附属医院就诊且被诊断为ICPP的110例6～9岁女童为研究对象。根据女童的年龄和体重指数(BMI)相匹配,选取110名健康女童作为对照组。检测所有女童尿BPA浓度,并测试其与ICPP风险的关系。实验室检查包括血清雌二醇(E2)水平,基础和促性腺激素释放激素(GnRH)刺激的促黄体激素(LH),促卵泡激素(FSH)水平,骨龄(BA),子宫和卵巢大小。结果 ICPP组和对照组的尿BPA中位数浓度分别为6.25 μg/g Cr和1.07 μg/g Cr(Z=-3.845,P<0.001)。调整混杂因素后,与BPA浓度最低的女童相比,最高浓度女童ICPP风险是其9.07倍(OR=9.07,95％CI:2.82～29.14) 。在ICPP组中,尿BPA浓度与FSH基础水平(r=-0.235,P=0.005)或FSH峰值水平(r=-0.171,P=0.044)呈负相关。结论 BPA暴露与学龄女童ICPP风险升高有关,潜在的机制可能归因于相对较低的FSH水平。     

Urinary phthalate metabolite and bisphenol A levels in the Korean adult population in association with sociodemographic and behavioral characteristics: Korean National Environmental Health Survey (KoNEHS) 2012–2014

BackdgroundPhthalates and bisphenol A (BPA) have been used in a variety of consumer products and are detected widely in both humans and the environment. Demographic and socio-economic characteristics that affect exposure to these chemicals have been investigated among several general populations; however, nationally-representative population-based studies are limited to Canada, Germany, and the USA. Moreover, relatively little is known about the socio-demographic characteristics that influence exposure to these chemicals among nationally representative populations of Asia.MethodsData are obtained from the Korean National Environmental Health Survey (2012–2014). In total, 6,478 adults (aged 19 and older) were recruited and sampled for urinary levels of major phthalate metabolites and bisphenol A. In addition, demographic and socio-economic parameters were determined from questionnaire data and the characteristics associated with urinary concentrations of the target chemicals were assessed.ResultsUrinary levels of bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) metabolites of Korean adults were generally higher, but those of mono-benzyl phthalate (MBzP) were lower, and BPA were similar or higher than those reported from national biomonitoring programs in the United States and Canada. Similar to other nationally representative populations, females and older adults showed higher creatinine-adjusted phthalate metabolite and BPA levels among the Korean population. Meanwhile, monthly household income and education were negatively associated with urinary phthalate metabolites. Among personal care products, nail polish use was positively associated with both phthalate metabolites and BPA concentrations in urine.ConclusionOur observations based on a nationally representative population of Korea show that socio-demographic determinants for these urinary chemicals vary by country, and should be considered for developing appropriate mitigation measures and policies.     

Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes

Background

Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled “BPA-free.” Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.

Objectives

This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.

Methods

We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol.

Results

We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression.

Conclusions

Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.

Citation

Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environ Health Perspect 123:643–650; http://dx.doi.org/10.1289/ehp.1408989     

Demographic and dietary predictors of urinary bisphenol A concentrations in adults in Israel

Background

To date, there is scarce data on levels of exposure to bisphenol A (BPA) in the general population in Israel and the region. The goal of the current study was to measure urinary levels of BPA in the general adult population in Israel and to determine the demographic and dietary predictors of exposure.

Methods

We recruited 249 individuals (ages 20–74) from five different regions in Israel. We collected urine samples and questionnaire data including detailed dietary data and analyzed urine samples for BPA concentrations.

Results

Eighty nine percent of the study population had urinary BPA concentrations equal to or above the level of quantification (0.3 μg/L). Median creatinine adjusted BPA urinary concentrations in the study population (2.3 μg/g) were slightly higher than those reported for the general population in the US (1.76 μg/g) and Canada (1.47 μg/g), and were comparable to those reported for the general population in Belgium (2.25 μg/g) and Korea (2.09 μg/g). BPA concentrations were higher in Jews compared to Arab and Druze (prevalence ratio (PR) = 2.34; 95%CI 1.56–3.49), in individuals with higher education (PR = 1.70, 1.11–2.62), in individuals consuming mushrooms (PR = 2.08, 1.07–4.05), and in smokers (PR = 1.43, 1.00–2.05).

Conclusions

We found that the general adult population in Israel is widely exposed to BPA. Our findings on higher BPA levels in Jews compared to Arabs and Druze and in individuals with higher education highlights the fact that predictors of BPA exposure vary across populations.     

Long-term study of urinary bisphenol A in elementary school children

Objectives  Due to its industrial application and frequent use as a coating material for food containers, bisphenol A (4,4′-isopropylidenediphenol, BPA) is present in abundance in our environment. Data on intake levels of BPA are limited in preadolescent children in Japan. This study was designed to help us better understand the current state of BPA exposure in children in Japan. Methods  We followed first graders (n = 104) attending school in a Tokyo suburb from 1998 until the sixth grade (2003), during which time we collected a total of three morning urine samples. Urinary BPA was analyzed using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Results  Ninety-four children were followed for 5 years. Median urinary BPA level was 2.66 ng/mg creatinine (CRE) (range 0.9–38.9) at first grade (1998), 1.52 ng/mg CRE (0.4–11.8) at third grade (2000), and 0.66 ng/mg CRE (0.2–8.5) at sixth grade (2003), showing a significant decrease in urinary BPA levels over a 5-year follow-up study (p < 0.001). No significant difference was seen between boys and girls at each grade. Conclusions  Urinary levels of BPA were relatively low throughout the study period; however, as the study progressed, we observed a significant decline in levels, the reason behind which is not yet clear.     

Prenatal bisphenol A and birth outcomes: MOCEH (Mothers and Children's Environmental Health) study

Bisphenol A (BPA) is used primarily in the production of polycarbonate plastics and epoxy resins. Widespread exposure to BPA has created a great deal of concern regarding its potential adverse effects on human health.This study examined the relationship between prenatal BPA exposure and birth outcomes, including birth weight, birth length, and ponderal index considering gender difference.A multi-center birth cohort study, Mothers and Children's Environmental Health (MOCEH) has been established in Korea since 2006. Study subjects are 757 pregnant women from the original cohort, who had their urinary BPA level measured during the third trimester, as well as information on birth outcome, prior medical history, psychosocial status, health behavior, environmental exposure as well as socio-demographic characteristics. Regression analysis was performed to assess the effect of BPA on birth outcome.The geometric mean concentration of BPA in pregnant women was 1.29 μg/L (1.87 μg/g creatinine) during late pregnancy. Urinary BPA concentrations were shown to be higher in women with a higher income level. Univariate regression analysis revealed a significant association between BPA levels and birth weight. In adjusted analysis, the second tertile of maternal BPA exposure exhibited an increase in birth weight, relative to the first tertile (p = 0.04). These relationships were more pronounced in male neonates. Also, prenatal exposure to BPA was associated with an increase of ponderal index in total, and especially female neonates.This study shows that the association of prenatal exposure to BPA with anthropometric measures, such as birth weight and birth length, differed by gender. Further study is required to more fully elaborate this relationship between prenatal BPA exposure and birth outcome.     

Bisphenol A,Bisphenol S,and 4-Hydro?xyphenyl 4-Isopro?oxyphenyl?sulfone (BPSIP) in Urine and Blood of Cashiers

Background:

Bisphenol A (BPA) is a high-production-volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products, including cash register receipt paper; however, little is known about exposure of cashiers to BPA and alternative compounds in receipt paper.

Objective:

We determined whether handling receipt paper results in measurable absorption of BPA or the BPA alternatives bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP).

Methods:

Cashiers (n = 77) and non-cashiers (n = 25) were recruited from the Raleigh–Durham–Chapel Hill region of North Carolina during 2011–2013. Receipts were analyzed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2 hr after completing a shift) were compared with pre-shift samples. Levels of these compounds in urine from cashiers were compared to levels in urine from non-cashiers.

Results:

Each receipt contained 1–2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. The mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as to increase after a shift, but the mean post-shift concentrations were significantly higher than those in non-cashiers. BPSIP was detected more frequently in the urine of cashiers handling BPSIP receipts than in the urine of non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently.

Conclusions:

Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP.

Citation:

Thayer KA, Taylor KW, Garantziotis S, Schurman SH, Kissling GE, Hunt D, Herbert B, Church R, Jankowich R, Churchwell MI, Scheri RC, Birnbaum LS, Bucher JR. 2016. Bisphenol A, bisphenol S, and 4-hydro​xyphenyl 4-isopro​oxyphenyl​sulfone (BPSIP) in urine and blood of cashiers. Environ Health Perspect 124:437–444; http://dx.doi.org/10.1289/ehp.1409427     

Goitrogenic Anions,Thyroid-Stimulating Hormone,and Thyroid Hormone in Infants

Background

Environmental exposure of infants to perchlorate, thiocyanate, nitrate, might interfere with thyroid function. U.S. women with higher background perchlorate exposure have higher thyroid-stimulating hormone (TSH) and lower thyroxine (T₄). There are no studies with individual measures of thyroid function and these goitrogens available in infants.

Objective

We examined the association of urinary perchlorate, nitrate, iodide, and thiocyanate with urinary T₄ and TSH in infants and whether that association differed by sex or iodide status.

Methods

We used data and samples from the Study of Estrogen Activity and Development, which assessed hormone levels of full-term infants over the first 12 months of life. The study included 92 full-term infants between birth and 1 year of age seen up to four times. Perchlorate, thiocyanate, nitrate, and iodide were measured in 206 urine samples; TSH and T₄ and were measured in urines and in 50 blood samples.

Results

In separate mixed models, adjusting for creatinine, age, sex, and body mass index, infants with higher urinary perchlorate, nitrate or thiocyanate had higher urinary TSH. With all three modeled, children with higher nitrate and thiocyanate had higher TSH, but higher perchlorate was associated with TSH only in children with low iodide. Unexpectedly, exposure to the three chemicals was generally associated with higher T₄.

Conclusions

The association of perchlorate exposure with increased urinary TSH in infants with low urinary iodide is consistent with previous findings. Higher thiocyanate and nitrate exposure were also associated with higher TSH in infants.     

Urinary bisphenol A concentrations in pregnant women

Bisphenol A is a chemical that is present in a number of products and types of food packaging. Prenatal exposure to bisphenol A may cause behavioural changes in young children. The aim of this study was to investigate exposure to bisphenol A in pregnant Australian women as a surrogate of neonatal exposure. First morning void urine samples were collected from 26 pregnant women at around week 38 of gestation. Bisphenol A was detectable in 85% of the samples analysed. The median concentration in this group of women was 2.41 μg/L with a range of <LOD – 5.66 μg/L. Women experiencing their first pregnancy had slightly higher urinary bisphenol A concentrations, as did women with a pre-pregnancy BMI of <25, however these relationships did not reach significance. This study provides the first information on bisphenol A exposure in Australia and reveals that pregnant women have measured biological concentrations of urinary bisphenol A similar to those reported for pregnant women in other developed countries. Given the potential impacts of prenatal bisphenol A exposure, further research in this area is warranted.     

Prenatal and Postnatal Bisphenol A Exposure and Body Mass Index in Childhood in the CHAMACOS Cohort

Background: Bisphenol A (BPA), a widely used endocrine-disrupting chemical, has been associated with increased body weight and fat deposition in rodents.Objectives: We examined whether prenatal and postnatal urinary BPA concentrations were associated with body mass index (BMI), waist circumference, percent body fat, and obesity in 9-year-old children (n = 311) in the CHAMACOS longitudinal cohort study.Methods: BPA was measured in spot urine samples collected from mothers twice during pregnancy and from children at 5 and 9 years of age.Results: Prenatal urinary BPA concentrations were associated with decreased BMI at 9 years of age in girls but not boys. Among girls, being in the highest tertile of prenatal BPA concentrations was associated with decreased BMI z-score (β = –0.47, 95% CI: –0.87, –0.07) and percent body fat (β = –4.36, 95% CI: –8.37, –0.34) and decreased odds of overweight/obesity [odds ratio (OR) = 0.37, 95% CI: 0.16, 0.91] compared with girls in the lowest tertile. These findings were strongest in prepubertal girls. Urinary BPA concentrations at 5 years of age were not associated with any anthropometric parameters at 5 or 9 years, but BPA concentrations at 9 years were positively associated with BMI, waist circumference, fat mass, and overweight/obesity at 9 years in boys and girls.Conclusions: Consistent with other cross-sectional studies, higher urinary BPA concentrations at 9 years of age were associated with increased adiposity at 9 years. However, increasing BPA concentrations in mothers during pregnancy were associated with decreased BMI, body fat, and overweight/obesity among their daughters at 9 years of age.     

Childhood Exposure to Phthalates: Associations with Thyroid Function,Insulin-like Growth Factor I,and Growth

Background

Phthalates are widely used chemicals, and human exposure is extensive. Recent studies have indicated that phthalates may have thyroid-disrupting properties.

Objective

We aimed to assess concentrations of phthalate metabolites in urine samples from Danish children and to investigate the associations with thyroid function, insulin-like growth factor I (IGF-I), and growth.

Methods

In 845 children 4–9 years of age, we determined urinary concentrations of 12 phthalate metabolites and serum levels of thyroid-stimulating hormone, thyroid hormones, and IGF-I.

Results

Phthalate metabolites were detected in all urine samples, of which monobutyl phthalate was present in highest concentration. Phthalate metabolites were negatively associated with serum levels of free and total triiodothyronine, although statistically significant primarily in girls. Metabolites of di(2-ethylhexyl) phthalate and diisononyl phthalate were negatively associated with IGF-I in boys. Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes.

Conclusions

Our study showed negative associations between urinary phthalate concentrations and thyroid hormones, IGF-I, and growth in children. Although our study was not designed to reveal the mechanism of action, the overall coherent negative associations between urine phthalate and thyroid and growth parameters may suggest causative negative roles of phthalate exposures for child health.     

Prenatal exposure to bisphenol A and child wheeze from birth to 3 years of age

Background: Bisphenol A (BPA), an endocrine-disrupting chemical that is routinely detected in > 90% of Americans, promotes experimental asthma in mice. The association of prenatal BPA exposure and wheeze has not been evaluated in humans.Objective: We examined the relationship between prenatal BPA exposure and wheeze in early childhood.Methods: We measured BPA concentrations in serial maternal urine samples from a prospective birth cohort of 398 mother–infant pairs and assessed parent-reported child wheeze every 6 months for 3 years. We used generalized estimating equations with a logit link to evaluate the association of prenatal urinary BPA concentration with the dichotomous outcome wheeze (wheeze over the previous 6 months).Results: Data were available for 365 children; BPA was detected in 99% of maternal urine samples during pregnancy. In multivariable analysis, a one-unit increase in log-transformed creatinine-standardized mean prenatal urinary BPA concentration was not significantly associated with child wheeze from birth to 3 years of age, but there was an interaction of BPA concentration with time (p = 0.003). Mean prenatal BPA above versus below the median was positively associated with wheeze at 6 months of age [adjusted odds ratio (AOR) = 2.3; 95% confidence interval (CI): 1.3, 4.1] but not at 3 years (AOR = 0.6; 95% CI: 0.3, 1.1). In secondary analyses evaluating associations of each prenatal BPA concentration separately, urinary BPA concentrations measured at 16 weeks gestation were associated with wheeze (AOR = 1.2; 95% CI: 1.0, 1.5), but BPA concentrations at 26 weeks of gestation or at birth were not.Conclusions: Mean prenatal BPA was associated with increased odds of wheeze in early life, and the effect diminished over time. Evaluating exposure at each prenatal time point demonstrated an association between wheeze from 6 months to 3 years and log-transformed BPA concentration at 16 weeks gestation only.     

Fetal Growth and Prenatal Exposure to Bisphenol A: The Generation R Study

Background: Prenatal exposure to bisphenol A (BPA) has been associated with adverse birth outcomes, but findings of previous studies have been inconsistent.Objective: We investigated the relation of prenatal BPA exposure with intrauterine growth and evaluated the effect of the number of measurements per subject on observed associations.Methods: This study was embedded in a Dutch population-based prospective cohort study, with urine samples collected during early, mid-, and late pregnancy. The study comprised 219 women, of whom 99 had one measurement, 40 had two measurements, and 80 had three measurements of urinary BPA. Fetal growth characteristics were repeatedly measured by ultrasound during pregnancy and combined with measurements at birth. Linear regression models for repeated measurements of both BPA and fetal growth were used to estimate associations between urinary concentrations of creatinine-based BPA (BPA_CB) and intrauterine growth.Results: The relationship between BPA_CB and fetal growth was sensitive to the number of BPA measurements per woman. Among 80 women with three BPA measurements, women with BPA_CB > 4.22 μg/g crea (creatinine) had lower growth rates for fetal weight and head circumference than did women with BPA_CB < 1.54 μg/g crea, with estimated differences in mean values at birth of –683 g (20.3% of mean) and –3.9 cm (11.5% of mean), respectively. When fewer measurements were available per woman, the exposure–response relationship became progressively attenuated and statistically nonsignificant.Conclusion: Our findings suggest that maternal urinary BPA may impair fetal growth. Because previous studies have shown contradictory findings, further evidence is needed to corroborate these findings in the general population.     

Lithium in drinking water and thyroid function

Background

High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function.

Objectives

We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function.

Methods

Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T₄) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods.

Results

The median urinary lithium concentration was 3,910 μg/L (5th, 95th percentiles, 270 μg/L, 10,400 μg/L). Median plasma concentrations (5th, 95th percentiles) of T₄ and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T₄ [β for a 1,000-μg/L increase = −0.19; 95% confidence interval (CI), −0.31 to −0.068; p = 0.002] and positively associated with TSH (β = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T₄, β = −0.17; 95% CI, −0.32 to −0.015; p = 0.032; for TSH: β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T₄ (adjusted T₄ for a 1 μg/L increase: β = 0.041; 95% CI, 0.012 to 0.071; p = 0.006).

Conclusions

Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.